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Pivoting to an allogeneic version of this program currently in preclinical development.
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This study will be conducted to evaluate the safety, tolerability, cellular kinetics (CK), activity, and pharmacodynamics (PD) of NTLA-5001 in participants with Acute Myeloid Leukemia (AML).
This 2-part first in human (FIH) study is comprised of two open-label arms. It is a multi-center, Phase 1/2a study evaluating the safety and activity of NTLA-5001 in subjects with persistent or recurrent Acute Myeloid Leukemia after first-line or later therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: NTLA-5001 | Experimental | Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count <5%, administered by IV infusion following lymphodepleting chemotherapy. |
|
| Arm 2: NTLA-5001 | Experimental | Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count ≥5%, administered by IV infusion following lymphodepleting chemotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Arm 1: NTLA-5001 | Genetic | Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. Cyclophosphamide and Fludarabine will be administered on Day -5, -4, and -3 as intravenous infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Participants That Experienced Dose-limiting Toxicities (DLTs) | DLTs were defined as events with onset within 28 days of infusion. AEs were collected from time of informed consent through the Week 112 visit. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 24.0. Severity of AEs was assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 toxicity grading criteria. The measure reported below for the primary outcome consists of DLT data only. Adverse events are reported in the Adverse Event section of this presentation. | Primary DLT assessment from NTLA-5001 infusion up to 28 days post-infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood | Frequency of edited TCR transgene copy number in the peripheral blood of the participants was determined by droplet digital polymerase chain reaction (ddPCR). | From NTLA-5001 infusion up to 4 weeks post-infusion |
| Persistence of NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood |
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Inclusion Criteria (abbreviated):
Exclusion Criteria (abbreviated):
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site 2 | Los Angeles | California | 90095 | United States | ||
| Research Site 5 |
Six participants were enrolled in the study (signed informed consent and underwent leukapheresis), but only two participants were dosed (administered Dose Level 1).
A total of 6 participants were enrolled at 3 sites in one country. A total of 2 participants received the product at Dose Level 1 in the Dose Escalation phase. The first participant was enrolled on 17 December 2021 and the last participant was enrolled on 21 July 2022. Dose escalation phase did not proceed beyond Dose Level 1. Dose Expansion phase was not initiated.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow | Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1. |
| FG001 | Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| C1:DoseLevel1 Assignment |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 22, 2021 | Oct 5, 2023 |
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| Arm 2: NTLA-5001 | Genetic | Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. Cyclophosphamide and Fludarabine will be administered on Day -5, -4, and -3 as intravenous infusion. |
|
Persistence of edited TCR transgene copy in the peripheral blood of the participants determined by ddPCR. |
| From NTLA-5001 infusion up to 4 weeks post-infusion |
| Tumor Response in Participants With AML | Rate of objective response, where response is complete response without measurable residual disease (CRMRD-) (Arm 1). Rate of objective response, where response is CRMRD-, complete response, complete remission with incomplete hematologic recovery, morphologic leukemia-free state, and partial remission (Arm 2). | From NTLA-5001 infusion up to 4 weeks post-infusion |
| Response Duration in Participants With AML | Bone marrow results were planned to be used to determine the duration of response / remission (DOR) for subjects with objective response, from first response until MRD was measured above the lower level of detection for the central laboratory assay, or death from any cause, whichever occurred first (Arm 1). Bone marrow results were planned to be used to determine DOR for subjects with composite CR, from first response to progression or death due to any cause, whichever occurred first (Arm 2). | From NTLA-5001 infusion up to 4 weeks post-infusion |
| Disease Progression in Participants With AML | Bone marrow results were used to determine the time to clinical progression. Progressive disease was defined as an increase from baseline of at least 25% of bone marrow blasts or an absolute increase of at least 5,000 cells/μL in the number of circulating leukemia cells | From NTLA-5001 infusion up to 4 weeks post-infusion |
| Tampa |
| Florida |
| 33612 |
| United States |
| Research Site 1 | Boston | Massachusetts | 02114 | United States |
| Research Site 6 | Portland | Oregon | 97239 | United States |
| Research Site 3 | Houston | Texas | 77030 | United States |
| Research Site 4 | Milwaukee | Wisconsin | 53226 | United States |
| Research Site 10 | Leeds | United Kingdom |
| Research Site 8 | London | United Kingdom |
| Research Site 9 | London | United Kingdom |
| Research Site 7 | Manchester | United Kingdom |
Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1. |
| COMPLETED |
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| NOT COMPLETED |
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|
| C1:DoseLevel1 Dosed Participants (W1-16) |
|
|
| Cohort2:Dose Level 2 |
|
Five participants were enrolled in Arm 2, but only one was dosed.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow | Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. |
| BG001 | Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow | Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
| |||||||||||||||
| Height | Mean | Standard Deviation | cm |
| |||||||||||||||
| Weight | Mean | Standard Deviation | kg |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Participants That Experienced Dose-limiting Toxicities (DLTs) | DLTs were defined as events with onset within 28 days of infusion. AEs were collected from time of informed consent through the Week 112 visit. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 24.0. Severity of AEs was assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 toxicity grading criteria. The measure reported below for the primary outcome consists of DLT data only. Adverse events are reported in the Adverse Event section of this presentation. | The Safety Analysis Set (defined as all participants who received NTLA-5001) was used for this presentation. | Posted | Count of Participants | Participants | Primary DLT assessment from NTLA-5001 infusion up to 28 days post-infusion |
|
|
| |||||||||||||||||||||||||||||
| Secondary | Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood | Frequency of edited TCR transgene copy number in the peripheral blood of the participants was determined by droplet digital polymerase chain reaction (ddPCR). | The Cell Kinetics Analysis Set (defined as all participants who received NTLA-5001 and have at least one evaluable cell kinetics sample) was used for this presentation. | Posted | Mean | Standard Deviation | copy/ng gDNA | From NTLA-5001 infusion up to 4 weeks post-infusion |
|
| |||||||||||||||||||||||||||||
| Secondary | Persistence of NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood | Persistence of edited TCR transgene copy in the peripheral blood of the participants determined by ddPCR. | The Cell Kinetics Analysis Set (defined as all participants who received NTLA-5001 and have at least one evaluable cell kinetics sample) was used for this presentation. | Posted | Number | Days | From NTLA-5001 infusion up to 4 weeks post-infusion |
|
| ||||||||||||||||||||||||||||||
| Secondary | Tumor Response in Participants With AML | Rate of objective response, where response is complete response without measurable residual disease (CRMRD-) (Arm 1). Rate of objective response, where response is CRMRD-, complete response, complete remission with incomplete hematologic recovery, morphologic leukemia-free state, and partial remission (Arm 2). | The Safety Analysis Set (defined as all participants who received NTLA-5001) was used for presentations of disease response data. | Posted | Count of Participants | Participants | From NTLA-5001 infusion up to 4 weeks post-infusion |
|
| ||||||||||||||||||||||||||||||
| Secondary | Response Duration in Participants With AML | Bone marrow results were planned to be used to determine the duration of response / remission (DOR) for subjects with objective response, from first response until MRD was measured above the lower level of detection for the central laboratory assay, or death from any cause, whichever occurred first (Arm 1). Bone marrow results were planned to be used to determine DOR for subjects with composite CR, from first response to progression or death due to any cause, whichever occurred first (Arm 2). | The Safety Analysis Set (defined as all participants who received NTLA-5001) was used for presentations of disease response data. | Posted | Median | Standard Deviation | Weeks | From NTLA-5001 infusion up to 4 weeks post-infusion |
| ||||||||||||||||||||||||||||||
| Secondary | Disease Progression in Participants With AML | Bone marrow results were used to determine the time to clinical progression. Progressive disease was defined as an increase from baseline of at least 25% of bone marrow blasts or an absolute increase of at least 5,000 cells/μL in the number of circulating leukemia cells | The Safety Analysis Set (defined as all participants who received NTLA-5001) was used for presentations of disease response data. | Posted | Median | Standard Deviation | Weeks | From NTLA-5001 infusion up to 4 weeks post-infusion |
|
|
From the date of NTLA-5001 infusion up to 16 weeks post-infusion.
Safety population = all participants who received NTLA-5001.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow | Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1. | 1 | 1 | 0 | 1 | 1 | 1 |
| EG001 | Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow | Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1. | 1 | 1 | 1 | 1 | 1 | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 24.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 24.0 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA version 24.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 24.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 24.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA version 24.0 | Systematic Assessment |
| |
| Herpes simplex reactivation | Infections and infestations | MedDRA version 24.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA version 24.0 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA version 24.0 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA version 24.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA version 24.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA version 24.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA version 24.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Systematic Assessment |
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| Hallucination | Psychiatric disorders | MedDRA version 24.0 | Systematic Assessment |
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| Affect lability | Psychiatric disorders | MedDRA version 24.0 | Systematic Assessment |
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| Abnormal dreams | Psychiatric disorders | MedDRA version 24.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA version 24.0 | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA version 24.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Systematic Assessment |
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| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Systematic Assessment |
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| Skin mass | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA version 24.0 | Systematic Assessment |
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The study was terminated by the Sponsor due to a strategic business decision.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Manager | Intellia Therapeutics | 833-888-0387 | clinicalscience@intelliatx.com |
| Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 6, 2023 | Oct 5, 2023 | SAP_002.pdf |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D007938 | Leukemia |
| D009369 | Neoplasms |
| D007154 | Immune System Diseases |
| D007160 | Immunoproliferative Disorders |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D009370 | Neoplasms by Histologic Type |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
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| Participants |
|
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| Units | Counts |
|---|---|
| Participants |
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| Participants |
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